Abstract

Protégé was a Phase 3, randomized, double-blind, parallel, placebo-controlled 2-year study of three intravenous teplizumab
dosing regimens, administered daily for 14 days at baseline and again after 26 weeks, in new-onset type 1 diabetes. We sought
to determine efficacy and safety of teplizumab immunotherapy at 2 years, and to identify characteristics associated with therapeutic
response. Of 516 randomized patients, 513 were treated, and 462 completed 2 years follow-up. Teplizumab (14-day full-dose)
reduced the loss of C-peptide mean AUC (a pre-specified secondary endpoint) at 2 years versus placebo. In analyses of pre-specified
and post-hoc subsets at entry, US residents, patients with C-peptide mean AUC >0.2nmol/L, those randomized ≤6 weeks after
diagnosis, HbA1c <7.5% (58 mmol/mol), insulin use <0.4U/kg/day, and ages 8-17 each had greater teplizumab-associated C-peptide preservation
than their counterparts. Exogenous insulin needs tended to be reduced versus placebo. Anti-drug antibodies developed in some
patients without apparent change in drug efficacy. No new safety or tolerability issues were observed during Year 2. In summary,
anti-CD3 therapy reduced C-peptide loss 2 years after diagnosis using a tolerable dose.